Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization.
Mechanisms of cellular iron sensing, regulation of erythropoiesis and mitochondrial iron utilization.
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DOI：
10.1053/j.seminhematol.2021.06.001
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发表时间：
2021-07
影响因子：
3.6
通讯作者：
Rouault TA
中科院分区：
文献类型：
--
作者：
Maio N;Zhang DL;Ghosh MC;Jain A;SantaMaria AM;Rouault TA
为了维持血红蛋白合成和基本代谢功能所需的足够铁供应，同时抵消铁毒性，人类和其他脊椎动物已经进化出有效的机制来保存和精细调节铁浓度、储存和组织分布。在全身水平，铁调节激素铁调素由肝脏响应血清铁水平和炎症而分泌。铁调素调节唯一已知的哺乳动物铁输出蛋白ferroportin的表达，以控制铁的膳食吸收、储存和组织分布。在细胞水平上，铁调节蛋白1和2（IRP1和IRP2）记录细胞溶质铁浓度，并转录后调节铁代谢基因的表达，以优化铁的可用性，用于基本的细胞过程，包括血红素生物合成和铁硫簇生物合成。影响铁传感机制或利用细胞中铁的主要途径的遗传故障引起广泛的人类疾病，其中一些疾病的特征在于线粒体铁积累。这篇综述将讨论系统和细胞铁传感的机制，重点是细胞中的主要铁利用途径，以及控制铁稳态的调节轴功能受损引起的人类疾病。
To maintain an adequate iron supply for hemoglobin synthesis and essential metabolic functions while counteracting iron toxicity, humans and other vertebrates have evolved effective mechanisms to conserve and finely regulate iron concentration, storage, and distribution to tissues. At the systemic level, the iron-regulatory hormone hepcidin is secreted by the liver in response to serum iron levels and inflammation. Hepcidin regulates the expression of the sole known mammalian iron exporter, ferroportin, to control dietary absorption, storage and tissue distribution of iron. At the cellular level, iron regulatory proteins 1 and 2 (IRP1 and IRP2) register cytosolic iron concentrations and post-transcriptionally regulate the expression of iron metabolism genes to optimize iron availability for essential cellular processes, including heme biosynthesis and iron-sulfur cluster biogenesis. Genetic malfunctions affecting the iron sensing mechanisms or the main pathways that utilize iron in the cell cause a broad range of human diseases, some of which are characterized by mitochondrial iron accumulation. This review will discuss the mechanisms of systemic and cellular iron sensing with a focus on the main iron utilization pathways in the cell, and on human conditions that arise from compromised function of the regulatory axes that control iron homeostasis.
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影响因子：
29
作者：
Anderson SA;Nizzi CP;Chang YI;Deck KM;Schmidt PJ;Galy B;Damnernsawad A;Broman AT;Kendziorski C;Hentze MW;Fleming MD;Zhang J;Eisenstein RS
通讯作者：
Eisenstein RS
影响因子：
15.9
作者：
Crispin, Andrew;Guo, Chaoshe;Ducamp, Sarah
通讯作者：
Ducamp, Sarah
影响因子：
4.8
作者：
Abboud, S;Haile, DJ
通讯作者：
Haile, DJ
影响因子：
20.3
作者：
Chen, Wen;Dailey, Harry A.;Paw, Barry H.
通讯作者：
Paw, Barry H.
影响因子：
20.3
作者：
Aschemeyer, Sharraya;Qiao, Bo;Nemeth, Elizabeta
通讯作者：
Nemeth, Elizabeta